Didn't show effects in RCTs; tied to BMI boost in cohort studies

Artificial sweeteners don't appear to have any significant effects on body mass index (BMI), according to a review and meta-analysis.

In randomized controlled trials, these sweeteners had no effects on BMI, and in cohort studies, they were actually associated with a modest increase in BMI, Meghan Azad, PhD, of the University of Manitoba in Canada, and colleagues reported in CMAJ.

"Evidence from [randomized controlled trials] does not clearly support the intended benefits of nonnutritive sweeteners for weight management," the researchers wrote. "In contrast, observational data suggest that routine consumption of nonnutritive sweeteners may be associated with a long-term increase in BMI and elevated risk of cardiometabolic disease."

They noted, however, that these associations haven't been confirmed in experimental studies and may be influenced by publication bias.

In 2008, nearly a third of Americans consumed nonnutritive sweeteners -- including aspartame, sucralose, and stevia -- on a daily basis. To assess whether regular consumption of these sweeteners was actually associated with long-term adverse cardiometabolic effects, Azad and colleagues conducted a review and meta-analysis involving 7 randomized controlled trials totaling 1,003 participants (three of which were funded by industry) and 30 cohort studies totaling 405,907 participants. The median follow-up was 6 months for the RCTs, and 10 years for the cohort studies.

In a selection of the trials totaling 242 participants, nonnutritive sweeteners had no significant effect on BMI (mean difference –0.37 kg/m2, 95% CI –1.10 to 0.36) -- and in a selection of the cohort studies totaling 21,256 participants, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03-0.06).

"Overall, there was limited evidence for the effect of non-nutritive sweeteners on BMI, with three long-term cohort studies suggesting a modest increase in BMI that was not confirmed in two RCTs," they wrote.

Trial data did not reveal any consistent effects of nonnutritive sweeteners on other measures of body composition. In the cohort studies, artificial sweeteners were associated with increases in weight and waist circumference and a higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes, and cardiovascular events.

Among the five RCTs that evaluated the use of nonnutritive sweeteners in obese participants, there was no consistent effect on change in weight (standardized MD –0.17, 95% CI –0.54 to 0.21). Two longer trials showed significant weight loss over 16 to 24 months of the intervention (standardized MD –0.55, 95% CI –0.75 to –0.34), and three six-month trials showed no effect for the use of nonnutritive sweeteners (standardized MD 0.13, 95% CI –0.34 to 0.59).

The researchers noted that the weight-loss effects of artificial sweeteners tended to be stronger in trials that were sponsored by industry than in those that were not.

Azad and colleagues called for more research into the topic, including comparing nonnutritive sweeteners against one another and evaluating the net effect of substituting nonnutritive sweeteners for sugar.

"Caution is warranted until the long-term health effects of artificial sweeteners are fully characterized," Azad said in a statement. "Given the widespread and increasing use of artificial sweeteners, and the current epidemic of obesity and related diseases, more research is needed to determine the long-term risks and benefits of these products."

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